Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Measurements of prostaglandin E2 (PGE2)-induced adenylyl cyclase activity in membranes isolated from epididymal rat adipocytes revealed inhibition of cAMP production at low concentrations of PGE2 (less than 10 mM) and stimulation at higher concentrations. This biphasic effect of PGE2 was obtained when adenylyl cyclase was stimulated with GTP or NaF. In the presence of forskolin only the inhibitory phase by PGE2 was observed. Sulprostone, a PGE2 analogue, did not affect cAMP synthesis in the presence of either GTP or NaF; however, in the presence of forskolin, it inhibited cAMP production similarly to PGE2. Treatment of the membranes with cholera or pertussis toxin did not alter the biphasic effect of PGE2 on cAMP production. These findings raise the possibility that PGE2 acts through several receptor subtypes which are coupled to GTP binding proteins different from the classical Gi or Gs proteins.
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PMID:Prostaglandin E2 can bimodally inhibit and stimulate the epididymal adipocyte adenylyl cyclase activity. 151 Aug 80

The group of prostaglandin (PG) E2- and prostacyclin receptors consists of different subtypes, which exhibit different affinities for prostaglandins and synthetic analogues. PGE2 activities the E-type PG receptor subtypes EP1, EP2 and EP3, whereas the PGE2 analogue, sulprostone, binds only to the EP1 and EP3 receptor subtypes. The stable PGI2 analogues, iloprost and cicaprost, both activate the PGI2 receptor (IP) and iloprost, additionally, bind to the EP1 subtype. Using these subtype-selective PG receptor agonists, we studied the interaction of PG receptor subtypes with Gs and Gi-type heterotrimeric guanine nucleotide-binding proteins (G proteins) in membranes from the human erythroleukaemia cell line, HEL. Sulprostone stimulated high-affinity GTPase in HEL membranes in a pertussis toxin (PTX)-sensitive manner. In contrast, the stimulations induced by PGE2, iloprost and cicaprost were only partially inhibited by PTX. PGE2, sulprostone, iloprost and cicaprost stimulated cholera toxin-catalysed ADP-ribosylation as well as labelling with GTP azidoanilide of membrane proteins comigrating with immunologically identified Gi protein alpha subunits. Furthermore, PGE2, iloprost and cicaprost enhanced GTP azidoanilide-labelling of Gs protein alpha subunits, whereas sulprostone did not. We suggest that in HEL cells (1) EP1 and EP3 receptor subtypes activate G1 proteins, that (2) the EP2 receptor subtype activates Gs proteins and that (3) the IP receptor activates both Gi and Gs proteins.
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PMID:Differential activation of Gi and Gs proteins by E- and I-type prostaglandins in membranes from the human erythroleukaemia cell line, HEL. 753 11

Prostaglandin E2 (PGE2) is the major renal cyclooxygenase metabolite of arachidonic acid. Urinary excretion of PGE2 is increased by dietary salt restriction, as well in cirrhosis and congestive heart failure. To determine whether urinary PGE2 affects transport along the nephron, the actions of luminal PGE2 were studied in the isolated perfused rabbit cortical collecting duct (CCD). Luminal PGE2 transiently hyperpolarized transepithelial voltage (Vt) in a dose-dependent manner (half-maximal effect approximately 10(-8) M) in contrast to a sustained depolarization of Vt produced by basolateral PGE2. Luminal PGE2 (0.1 microM) also significantly stimulated osmotic water permeability in the CCD. In CCDs cultured on semipermeable supports, apical PGE2 stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, suggesting the effects of luminal PGE2 are mediated by adenylyl cyclase-stimulating EP2 or EP4 receptors. Sulprostone, a PGE2 analogue selective for EP1 and EP3 receptors, affected Vt only when applied from the basolateral but not the luminal surface. Luminal application of the EP2 receptor agonist butaprost was also without effect. These results suggest that luminal PGE2 affects Vt via a butaprost-insensitive EP4 receptor. The Vt effect of luminal PGE2 was not blocked by pertussis toxin, also arguing against an EP3-mediated Gi-coupled effect. Finally, 1 microM luminal PGE2 only slightly increased CCD intracellular calcium concentration ([Ca2+]i), in contrast to the marked increase in [Ca2+]i produced by basolateral PGE2 (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Luminal prostaglandin E receptors regulate salt and water transport in rabbit cortical collecting duct. 765

Prostaglandin E2 (PGE2) modulates both water and sodium transport in the rabbit cortical collecting duct (CCD). To determine whether these effects are mediated by separate PGE2 receptors, we compared the effects of PGE2 and its analogue sulprostone in the isolated perfused rabbit CCD. PGE2 increased basal water permeability (hydraulic conductivity), whereas sulprostone did not. PGE2 and sulprostone were equipotent inhibitors of water absorption when it was prestimulated by vasopressin. Pertussis toxin completely reversed the inhibitory effect of sulprostone but only partially reversed the inhibitory effect of PGE2. In contrast, a protein kinase C (PKC) inhibitor, staurosporine, partially reversed the inhibitory effect of PGE2 but had no effect on sulprostone. PGE2 also raised intracellular calcium ([Ca2+]i). This effect is coupled to its capacity to inhibit Na+ absorption. Sulprostone was 10-fold less potent than PGE2 both in raising [Ca2+]i or inhibiting sodium transport. The results suggest sulprostone selectively interacts with a PGE2 receptor coupled to pertussis toxin-sensitive inhibition of water permeability. Sulprostone less potently activates a PGE2 receptor coupled to [Ca2+]i, PKC activation, and sodium transport and completely fails to interact with the PGE2 receptor that stimulates water permeability in the collecting duct. These results suggest distinct PGE2 receptors modulate sodium and water transport in the CCD.
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PMID:Evidence that separate PGE2 receptors modulate water and sodium transport in rabbit cortical collecting duct. 823 44

Prostaglandins (PGs) exert their effects via binding to specific cell surface receptors and influencing second messenger systems through G-proteins. PGE2 may interact with at least four receptor subtypes (EP1, EP2, EP3, EP4), each showing different pharmacological profiles. The second messengers calcium, inositol phosphates (InsPs) and cyclic nucleotides play decisive roles in uterine contractility. The question in this investigation was, which EP receptors, G-proteins and second messenger systems transmit PGE2 induced signals in human myometrium. We have measured changes in InsPs and cAMP formation and also in intracellular calcium concentration ([Ca2+]i) induced by PGE2 and receptor subtype selective analogues in cultured human myometrial cells. PGE2 increased cAMP level and this effect was shared by the EP2 receptor subtype selective agonist Butaprost and by Misoprostol (EP3 > EP2 > EP1). Sulprostone (EP3 > EP1) did not stimulate adenylyl cyclase activity per se, but inhibited forskolin-stimulated adenylyl cyclase in a pertussis toxin (PT) sensitive way. PGE2, GR63799X (EP3 selective), Sulprostone and Misoprostol activated phospholipase-C (PLC), this effect was resistant to PT treatment. PGE2 also elevated [Ca2+]i from the resting level of 60-90 nM up to 350 nM. Low concentrations (1-300 nM) of PGE2 increased [Ca2+]i without PLC activation. The selective EP1 inhibitor AH6809, Nifedipine, Verapamil and PT treatment inhibited this effect of PGE2. In cultured human myometrial cells PGE2 interacts with EP1 receptors, which elevate [Ca2+]i independently from PLC, but involving a Gi protein and plasmamembrane calcium channels; EP2 receptors which stimulate adenylyl cyclase; EP3A receptors, which inhibit adenylyl cyclase activity through Gi activation and EP3D receptors which activate PLC through a PT-insensitive pathway and also elevate [Ca2+]i.
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PMID:Prostaglandin E receptors in myometrial cells. 953 Apr 35

1. The aim of the present study was to investigate the transduction pathways elicited by prostaglandin E2 (PGE2) to inhibit hormone-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in the outer medullary collecting duct (OMCD) and medullary thick ascending limb (MTAL) microdissected from the rat nephron. 2. In the OMCD, 0.3 microM PGE2 and low concentrations of Ca2+ ionophores (10 nM ionomycin or 50 nM A23187) inhibited by about 50% a same pool of arginine vasopressin (AVP)-stimulated cyclic AMP content through a same process insensitive to Bordetella pertussis toxin (PTX). 3. Sulprostone, an agonist of the EP1/EP3 subtypes of the PGE2 receptor, decreased AVP-dependent cyclic AMP accumulation in OMCD and MTAL samples. The concentration eliciting half-maximal inhibition was of about 50 nM in OMCD and 0.1 nM in MTAL. 4. In MTAL, 1 nM sulprostone and PGE2 inhibited by about 90% a same pool of AVP-dependent cyclic AMP content through a PTX-sensitive, Ca2+ -independent pathway. 5. In the OMCD, PGE2 decreased by about 50% glucagon-dependent cyclic AMP synthesis by a process sensitive to PTX and Ca2+ -independent. Sulprostone 1 nM induced the same level of inhibition. 6. These results demonstrate that PGE2 decrease hormone-dependent cyclic AMP accumulation through a G(alpha)i-mediated inhibition of adenylyl cyclase activity in MTAL cells and glucagon-sensitive cells of the OMCD or through a PTX-insensitive increase of intracellular Ca2+ concentration in AVP-sensitive cells of the OMCD.
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PMID:Cell-specific coupling of PGE2 to different transduction pathways in arginine vasopressin- and glucagon-sensitive segments of the rat renal tubule. 1019 86